tbuckley/cabot-search huggingface dataset:
A prospective trial of apalutamide and abiraterone acetate plus prednisone in Black and White men with metastatic castrate-resistant prostate cancer.
Authors: Daniel J. George, Susan Halabi, Mark T. Fleming, Elisabeth I. Heath, Ronald F. Tutrone, Linda Sutton, Young E. Whang, Brian E. Lewis, Michael Sandon Humeniuk, William R. Berry, Michael Roger Harrison, Julia Hurrelbrink, Kellie Shobe, Julia Rasmussen, Monika Anand, Marco Reyes-Martinez, Lauren Howard, Steven R. Patierno, Jennifer A Freedman, Andrew J. Armstrong
Journal: Journal of Clinical Oncology (2023)

5015 Background: Abi Race was the first prospective parallel cohort study of abiraterone acetate plus prednisone (AAP) in Black and White men with metastatic castrate-resistant prostate cancer (mCRPC) and demonstrated greater prostate-specific antigen (PSA) response, time to PSA progression (TTP) and toxicity rates among Black patients (pts). We designed the PANTHER trial to estimate clinical outcomes among Black and White pts with mCRPC treated with apalutamide, abiraterone, plus prednisone. Methods: This parallel cohort multicenter study treated androgen receptor pathway inhibitor naïve mCRPC pts with oral apalutamide (240 mg/d), abiraterone (1000 mg/d) and prednisone (10 mg/d) (AAAP) continuously until disease progression, unacceptable toxicity or 2 years. The primary endpoint was radiographic progression free survival (rPFS); secondary endpoints were to estimate TTP, overall survival (OS) and best PSA response, among Black and White pts, separately. Exploratory endpoints included safety and correlative biomarkers of outcome by race and ancestry. Results: Between July 2017 and January 2021, we enrolled 43 Black and 50 White pts from 8 sites. Baseline prognostic characteristics were largely similar with some differences. We report an interim analysis as the pts are still followed for OS. At the time of the abstract submission, there were 18 and 36 rPFS events and 15 and 30 deaths in Black and White pts, respectively. We present the time to event endpoint rates at 12 and 24 mos and PSA declines for Black and White pts. Conclusions: We hypothesize that treatment with the combination of AAAP may result in clinical efficacy in Black men with mCRPC. Black pts were underrepresented in the phase III ACIS trial which compared AAP to AAAP and demonstrated longer rPFS but not OS. Further studies of AAAP combination therapy among Black men with advanced prostate cancer are needed to determine potential clinical benefits in this understudied population. Clinical trial information: NCT03098836 . [Table: see text]
Single cell transcriptomics to identify immunological ACKR1<sup>+</sup> DCs and their effect on clinical outcomes in left-sided CRC.
Authors: Qian Wang, Tongqiang Fan, Tao Wang, Shanshan Xiao
Journal: Journal of Clinical Oncology (2023)

e15550 Background: Myeloid cells play critical roles in the growth and metastasis of malignant tumors with both protumor and antitumor capabilities. Plenty of studies have reported they participated in modulating tumor inflammation and angiogenesis, and therapeutic strategies targeting myeloid cells are ongoing in pre-clinical and clinical trials. The functions of myeloid cells and their subtypes in left-sided and right-side CRC remain unclear. Methods: A published scRNA-seq dataset (Pelka et al., 2021) with 21 samples from left-sided CRC and 79 from right-sided CRC (colorectal cancer) was obtained. Seurat (Stuart et al., 2019) was used to perform dimensionality reduction and differential expression analysis, and the cell subtypes in the myeloid cells were identified to study the associations between clinical outcomes and different tumor tissue sites of CRC. We also obtained an immunotherapy dataset from TISMO to identify associations between cell subtypes and immunotherapy outcomes. Results: Systematic comparisons of myeloid cells (n = 39,167) from left-sided and right-sided CRC revealed that highly expressed genes from right-sided CRC showed protumor capability and those from left-sided CRC showed antitumor activity. Specifically, left-sided CRC harbored a significant (p = 0.018) higher proportion of ACKR1 + DCs compared to right-sided CRC. ACKR1 + DCs might be immunological as its marker genes were significantly positively correlated with CD8+T cells and highly enriched in APC(antigen processing presentation)-related pathways. TCGA survival analysis revealed that the higher expression of the marker genes in ACKR1 + DC was associated with better overall survival (OS, p = 0.0088). Furthermore, immunotherapy biopsy showed ACKR1 + DCs subtype significantly enriched in immunotherapy responsive group compared to non-responsive group in colon cancer (p = 0.019), melanoma (p = 0.0058) and renal adenocarcinoma (p = 3.3e-06) among the obtained TISMO dataset. Conclusions: We identified an immunological ACKR1 + DCs subtype, which was highly enriched in left-sided CRC and was correlated with better clinical outcomes and immunotherapy responses. Those findings might provide potential therapeutic target and help better understand the mechanism of treatment strategies in CRC.
Tumor immunity portrait: An AI-driven molecular predictor combining tumor microenvironment and tumor mutational burden for immune checkpoint inhibitor response prediction.
Authors: Polina Shilo, Artem Tarasov, Anna Filatova, Konstantin Danilov, Ivan Valiev, Nikita Kotlov, Jessica H. Brown, Anna Ogloblina, Alexander Bagaev, Nathan Fowler
Journal: Journal of Clinical Oncology (2023)

e14691 Background: Low response rates and toxicities from immune checkpoint inhibitors (ICI) highlight the need for improved ICI response prediction tools. Increasing evidence shows the tumor microenvironment (TME) plays a critical role in therapy response; however, current ICI response prediction methods often use a single tumor characteristic (i.e., tumor mutational burden [TMB]). Here, we present the BostonGene Tumor Immunity Portrait, an AI-driven molecular predictor based on the TME subtype combined with TMB status to identify ICI responders in non-small cell lung cancer (NSCLC), melanoma, and gastric cancer (GC). Methods: We collected a meta cohort from 26 publicly available datasets (n = 2,077) composed of NSCLC, melanoma, and GC patients that received ICI therapy. A transcriptomic-based TME subtyping approach was used to classify the TME as fibrotic (F), immune-enriched, fibrotic (IE/F), immune-enriched (IE), or desert (D) (Bagaev, Cancer Cell, 2021). TMB status (low &lt; 10; high &gt; 10) was determined by whole exome sequencing. A logistic regression model was used to generate a score of 0, 1, 2, or 3 based on the sum of points assigned to the TME subtype (F = 0 points, IE/F and D = 1 point, IE = 2 points) and to the TMB status (high = 1 point and low = 0 points). Each score corresponded to one of four Tumor Immunity Portrait types: 0 - Immunosuppressive; 1 - Resistant; 2 - Neutral; 3 - Immune Primed. Results: Tumor Immunity Portrait types were associated with increasing ICI response rates in each cancer type. Immune Primed type (IE + TMB-High) response rates in melanoma and GC were 76.2% and 100%, respectively. Immunosuppressive type (F + TMB-Low) was associated with ICI non-response in melanoma (p = 0.003) and NSCLC (p &lt; 0.001). The Tumor Immunity Portrait accurately predicted ICI non-response, shown by the negative predictive value (NPV) of the Immunosuppressive type (F + TMB-Low) for NSCLC (100%), melanoma (92.3%), and GC (96.1%). Conclusions: Using an integrated approach combining the tumor’s characteristics and TME, the BostonGene Tumor Immunity Portrait provides accurate prediction of ICI non-response in 3 cancer types, warranting further validation for use in personalized treatment decision making. [Table: see text]
Real-world baseline characteristics and first-line (1L) treatment (Tx) in patients (pts) with de novo metastatic castration-sensitive prostate cancer (mCSPC) by disease volume.
Authors: Stephen J. Freedland, Agnes Hong, Nader N. El-Chaar, Amanda Marie De Hoedt, Janet Kim, Krishnan Ramaswamy, Lin Gu, Thomas Polascik
Journal: Journal of Clinical Oncology (2023)

e17081 Background: Intensification of androgen deprivation therapy (ADT) using novel hormonal therapies (NHT) has been established as a new standard of care for pts with mCSPC. Tx intensification still remains suboptimal, and data in de novo mCSPC pts is limited. Moreover, prior studies utilized claims data and so could not assess the impact of disease burden on Tx intensification. This study assessed baseline characteristics and 1L Tx patterns in pts with high-volume (HV) vs low-volume (LV) de novo mCSPC. Methods: This retrospective study used the Veterans Affairs Informatics and Computing Infrastructure to identify adult men who had ≥1 ICD code for prostate cancer and de novo mCSPC diagnosed between February 2018 and June 2020 confirmed by clinical chart review and initiated either ADT alone, ADT + first-generation non-steroidal anti-androgens [NSAA], or ADT+NHT. Index date was defined as ADT initiation date. The volume of disease was defined as HV or LV per the CHAARTED trial criteria (presence of visceral metastasis and/or ≥4 bone metastases, with ≥1 metastasis beyond the pelvis and vertebral column). Clinical data was hand abstracted from the medical record. Baseline characteristics and 1L Tx were analyzed descriptively. Results: Of the 380 de novo mCSPC pts reviewed, 57% had HV and 43% had LV disease. Mean age of pts was similar between HV and LV cohorts, 74.5 vs 75.2 years, respectively. In addition, the proportion of Black vs White pts in the HV and LV cohorts was similar, 34% and 35% were Black, and 66% and 65% were White, respectively. At index date, HV pts had higher median prostate-specific antigen (153.1 ng/mL vs 73.8 ng/mL) and alkaline phosphatase (192.0 IU/L vs 106.0 IU/L) vs LV pts. HV pts were less likely to have diabetes and cardiovascular comorbidities than LV pts (Table); however, the distribution of Charlson Comorbidity Index score was similar between cohorts (mean [SD]: 4.4 [3.1] vs 4.2 [3.1]). Among the pts with bone metastases only, HV pts had higher proportion (65%) of “too numerous to count” bone metastases vs LV pts (9%). While ADT+NHT use was slightly more common among HV pts (35%) vs LV pts (27%), in both HV and LV cohorts, ADT±NSAA was the most common 1L Tx (Table). The median 1L Tx duration was shorter in the HV pts compared with the LV pts (286 vs 358 days). Conclusions: The results showed that Tx intensification was underutilized in de novo mCSPC pts, even among those with HV, pointing toward an unmet need among pts with de novo mCSPC regardless of disease burden. [Table: see text]
A study of cadonilimab combined with regorafenib as second-line or later therapy in patients with advanced hepatocellular carcinoma (aHCC).
Authors: Qi Qi, Yang Liu, Rentao Li, Yayue Liu, Xihao Zhang, Wei Lu, Huikai Li
Journal: Journal of Clinical Oncology (2023)

e16154 Background: Current second-line treatment options for aHCC patients (pts), including single TKI or anti-PD-1+anti-CTLA4, result in limited survival benefits, objective responses or increasing concerns regarding adverse effects. An exploration of safer and more effective second-line or later therapies for aHCC is paramount. Cadonilimab is a first-in-class bispecific, humanized IgG1 antibody targeting PD-1 and CTLA-4, which has the potential to boost immune surveillance in HCC. Previous data indicated that cadonilimab possesses an improved safety profile and an encouraging anti-tumour activity compared to combined administration of anti-PD-1 plus anti-CTLA-4 antibodies. Regorafenib was the first TKI that approved globally as a second-line treatment of aHCC. Here, we evaluated the safety of cadonilimab plus regorafenib as second-line or later therapy in pts with aHCC. Methods: The study population derived from prospectively collected retrospectively analyzed data (10/2022-02/2023) of pts treated with cadonilimab plus regorafenib as second-line or later therapy for aHCC at Tianjin Cancer Hospital Airport Hospital. The primary endpoint was safety. Results: We identified 29 pts with aHCC who received cadonilimab plus regorafenib. The median age was 59 years; 86.2% were male; 72% were ECOG PS 0; 72% had a Child-Pugh score of A at diagnosis. High risk factors for HCC included MVI (3pts), ≥3 tumour lesions (10pts), tumour diameter ≥5cm (5pts), AFP≥400ng/mL (5pts). Six pts (21%) received cadonilimab plus regorafenib in the second-line while the rest of pts (79%) received it as third-line or later. All pts previously received at least one line of immunotherapy combined with anti-angiogenic target agents. Seven pts received triple combination regimens (ICIs+TKIs/Bev+HAIC) before. At time of data extraction, no pts were assessed for efficacy due to the COVID-19 pandemic (especially the outbreak in early December 2022) and short follow-up time, we focused on the safety and tolerability in this report. Any grade treatment related adverse events (TRAEs) occurred in 24pts (83%). The most common TRAEs of any grade were hypoalbuminemia (24%), lymphocyte count decreased (21%), rash (14%), nausea (14%) and infusion reaction (14%). Only four (14%) patients experienced grade 3 TRAEs including infusion reaction (2pts), lymphocyte count decreased (1pt) and gastrointestinal hemorrhage (1pt, regorafenib related). No grade 4-5 TRAEs were observed. Conclusions: The combination of cadonilimab plus regorafenib was generally well tolerated. The prospective trail of cadonilimab combined with regorafenib as second-line or later therapy for aHCC is ongoing (NCT05644379). Although it needs to be reconfirmed, the treatment responses of some patients are encouraging (including sharp decrease in AFP level and/or reduced tumor size). Related data will be reported in the future.
Trastuzumab deruxtecan (T-DXd) in patients (pts) with HER2-overexpressing/amplified (HER2+) metastatic colorectal cancer (mCRC): Primary results from the multicenter, randomized, phase 2 DESTINY-CRC02 study.
Authors: Kanwal Pratap Singh Raghav, Salvatore Siena, Atsuo Takashima, Takeshi Kato, Marc Van Den Eynde, Maria Di Bartolomeo, Yoshito Komatsu, Hisato Kawakami, Marc Peeters, Thierry Andre, Sara Lonardi, Kensei Yamaguchi, Jeanne Tie, Cristina Gravalos Castro, John H Strickler, Daniel Barrios, Qi Yan, Takahiro Kamio, Kojiro Kobayashi, Takayuki Yoshino
Journal: Journal of Clinical Oncology (2023)

3501 Background: T-DXd (6.4 mg/kg, every 3 weeks [Q3W]) demonstrated antitumor activity in pts with HER2+ mCRC in DESTINY-CRC01 (Siena et al. Lancet Oncol. 2021). We present primary results of DESTINY-CRC02 (NCT04744831), which assessed the efficacy and safety of T-DXd (5.4 and 6.4 mg/kg) in pts with HER2+ mCRC. Methods: This was a multicenter phase 2 study. Eligible pts had centrally confirmed HER2+ (immunohistochemistry [IHC] 3+ or IHC 2+/in situ hybridization [ISH]+) mCRC. Pts with RAS wild-type (wt) or mutant (m) mCRC were eligible. Pts had received prior standard therapy, unless contraindicated; prior anti-HER2 therapy was allowed. In stage 1, 80 pts were randomized 1:1 to 5.4 (n = 40) or 6.4 (n = 40) mg/kg T-DXd Q3W. In stage 2, an additional 42 pts received 5.4 mg/kg T-DXd. Primary endpoint was confirmed objective response rate (cORR) by blinded independent central review (BICR). Secondary endpoints included duration of response (DoR), progression-free survival (PFS), overall survival (OS), and safety. Results: At data cutoff (Nov 1, 2022), most pts in the 5.4 and 6.4 mg/kg T-DXd arms had HER2 IHC 3+ (78.0% and 85.0%), RAS wt tumors (82.9% and 85.0%), and a median of 3 and 4 prior lines of therapy, respectively. cORR was 37.8% (95% CI, 27.3-49.2%) in the 5.4 mg/kg arm and 27.5% (95% CI, 14.6-43.9%) in the 6.4 mg/kg arm (all partial responses in both arms). Key efficacy data are shown in the Table: Grade ≥3 treatment-emergent adverse events (AEs) were observed in 41/83 pts (49.4%) and 23/39 pts (59.0%) in the 5.4 and 6.4 mg/kg T-DXd arms, respectively. Serious AEs were observed in 20/83 pts (24.1%) and 12/39 pts (30.8%) in the 5.4 and 6.4 mg/kg arms, respectively. Independently adjudicated drug-related interstitial lung disease occurred in 7/83 pts (8.4%) with 5.4 mg/kg T-DXd and 5/39 pts (12.8%) with 6.4 mg/kg T-DXd, and most events were grade 1/2 (1 grade 5 in the 6.4 mg/kg arm). Conclusions: T-DXd showed promising antitumor activity in pts with HER2+ mCRC at both 5.4 and 6.4 mg/kg doses. Antitumor efficacy was observed irrespective of RAS mutation status at 5.4 mg/kg T-DXd, and in those with prior anti-HER2 therapy. Overall, safety was consistent with the known safety profile of T-DXd and favored the 5.4 mg/kg dose. Clinical trial information: NCT04744831 . [Table: see text]
Impact of the COVID-19 pandemic on insurance transitions among commercially insured cancer patients in Washington state.
Authors: Scott David Ramsey, Qin Sun, Catherine R. Fedorenko, Aasthaa Bansal, Karma L. Kreizenbeck, Veena Shankaran
Journal: Journal of Clinical Oncology (2023)

6552 Background: Insurance transitions following cancer diagnosis can disrupt care and impact outcomes. The COVID-19 pandemic impacted employment for millions of Americans, threatening their ability to maintain insurance. Using a large database linking commercial insurance to cancer registry records, we evaluated insurance transitions among newly diagnosed cancer patients in the pre- and post-COVID periods. Methods: We linked Western Washington SEER cancer registry records and enrollment records from two commercial insurers covering 3 million persons and Medicaid in Washington State. Eligible persons were ages 18-63 and commercially insured in the 12 months prior to their first cancer diagnosis. Post-diagnosis follow-up periods were stratified into pre-COVID (January 2017 – February 2020) and post-COVID (March 2020 - December 2020). We created logistic regression models to look at factors associated with (1) disenrollment for any reason and (2) transition to Medicaid, accounting for age, sex, race, year of diagnosis, cancer site, AJCC stage, comorbidities, and Area Deprivation Index (ADI), and diagnosis during the pandemic. Results: Among 5,458 newly diagnosed solid tumor patients enrolled in commercial plans pre-COVID, 16.9% disenrolled for any reason over 12 months following diagnosis. Among disenrollees, 10.0% transitioned to Medicaid. Patients with Lung, Oral, and Myeloma cancers had the highest disenrollments (21.2%, 21.0%, and 19.3% respectively). Among the 1,224 diagnosed post-COVID, 9.7% disenrolled for any reason. Among those who disenrolled, 21.0% enrolled in Medicaid. Patients with Leukemia, Melanoma, Oral, and Gynecologic cancers had the highest disenrollments (23.3%, 14.5%, 13.6%, and 13.6% respectively). In logistic regression, persons diagnosed after the pandemic were less likely to disenroll compared to the pre-pandemic period (Table). Transitions to Medicaid was not greater post-Pandemic. Advanced stage, comorbidity, and living in high ADI regions were significantly associated with transitioning to Medicaid. Conclusions: Newly diagnosed cancer patients with commercial insurance during the COVID-19 pandemic were substantially less likely to disenroll than those diagnosed before the pandemic. The findings may reflect pandemic-related preferences for job stability during a time of personal and societal crisis. [Table: see text]
Treatment and outcomes of pancreatic cancer in Armenia: Hospital-based study.
Authors: Samvel Bardakhchyan, Sergo Mkhitaryan, Davit Zohrabyan, Liana Safaryan, Armen Avagyan, Lilit Harutyunyan, Jemma Arakelyan, Hovsep Gharadaghyan, Sahak Azizyan, Mariam Mailyan, Amalya Sargsyan, Martin Harutyunyan, Nune Karapetyan
Journal: Journal of Clinical Oncology (2023)

e16251 Background: Pancreatic cancer is one of the deadliest cancers in the world. In Armenia, pancreatic cancer is on the 12th place by incidence. The aim of this study is to evaluate treatment and outcomes of pancreatic cancer in Armenia during the last 12 years. Methods: For this retrospective hospital-based study we have collected data from three oncology centers in Armenia: “Muratsan” Hospital of Yerevan State Medical University, “Miqaelyan institute of surgery” and “Hematology center after prof. Yeolyan”. The information about patients with pancreatic cancer who were treated at these centers during 01/01/2010 - 01/01/2022 period was collected from the medical records. Log- rank test and Kaplan-Meier curves were used for survival analysis. Cox regression analysis was done for identification of main prognostic factors. Results: 70 patients with pancreatic cancer were involved in the final analysis. From them 44.3% were female. Median age at diagnosis was 63 years. Median follow up time was 10,5 months (range 2-146). 11,4% of patients had stage I-II, 27,1% stage III, 58,6% stage IV cancer. The main independent prognostic factor for overall survival (OS) was tumor grade, while TNM stage was not significant. 23% of patients were alive before study end date. Median OS was 12 months (range 2-146 months). Median overall survival was 35 months in stage I-II, 11 months in stage III and 11 months in stage IV. In stage I-III pancreatic cancer patients, those who had undergone surgery (44.4%) lived significantly longer (35 vs 11 months, p=0.011). 38.6% of patients received chemotherapy with Gemcitabine plus Capecitabine regimen, while 41.4% with FOLFIRINOX regimen. No significant difference in survival was found between these groups (11 vs 13 months, p=0.35). Conclusions: As our results has shown survival of pancreatic cancer patients in Armenia is dismal, not exceeding 1 year. Hopefully further research in the field and new treatment modalities will improve the situation.